Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy

Proteomics Clin Appl. 2013 Jun;7(5-6):316-26. doi: 10.1002/prca.201300004.


Purpose: Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage.

Experimental design: Label-free LC-MS/MS for protein biomarker discovery and MRM for targeted confirmation were applied to patient serum samples accrued in a non-interventional clinical trial of CHRT.

Results: Analysis of time-matched patient samples from a patient with disease recurrence compared with a time match disease-free individual supported the identification of 287 proteins. Of these, 141 proteins were quantified, 95 proteins changed in their expression (P ≤ 0.05 and ≥1.5-fold change) and of these 16 were selected for MRM confirmation. The protein expression changes observed in the label-free LC-MS/MS and MRM analysis were found to be highly correlated (R(2) = 0.85).

Conclusions and clinical relevance: The establishment of a clinical trial to support the acquisition of samples and development of a pipeline for MS-based biomarker discovery and validation should contribute to the identification of a serum protein signature to predict or monitor the outcome of treatment of patients with PCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Blood Proteins / analysis
  • Blood Proteins / metabolism
  • Chromatography, High Pressure Liquid*
  • Combined Modality Therapy
  • Humans
  • Male
  • Nanotechnology
  • Principal Component Analysis
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / radiotherapy
  • Recurrence
  • Tandem Mass Spectrometry*
  • Time Factors
  • Trypsin / metabolism


  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Blood Proteins
  • Trypsin